â: Treatment of multiple sclerosis with interferon Vectiveness and quality of life

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J Neurol Neurosurg Psychiatry 2000;68:144–149
Treatment of multiple sclerosis with interferon â:
an appraisal of cost-eVectiveness and quality of life
David Parkin, Ann Jacoby, Paul McNamee, Paul Miller, Simon Thomas, David Bates
Department of
Epidemiology and
Public Health, School
of Health Sciences,
University of
Newcastle, Newcastle
Upon Tyne, NE2 4HH,
D Parkin
P McNamee
Centre for Health
Services Research
A Jacoby
Wolfson Unit of
Department of
S Thomas
Department of
D Bates
Trent Institute for
Health Services
Research, The Medical
School, Queens
Medical Centre,
University of
P Miller
Correspondence to:
Paul McNamee, Department
of Epidemiology and Public
Health, School of Health
Sciences, University of
Newcastle, Newcastle Upon
Tyne, NE2 4HH, UK
[email protected]
Received 26 March 1999 and
in final form
10 September 1999
Accepted 17 September 1999
Objective—To evaluate the cost-eVectiveness of interferon beta-1b (IFâ-1b) for
relapsing-remitting multiple sclerosis
Methods—Construction of a cost-eVectiveness model using published data on
IFâ-1b eVectiveness and the natural history of RRMS, and new data on costs and
quality of life (QoL) from a sample of 102
patients with RRMS and resident in
northern England.
Results—Poorer QoL was found for patients with multiple sclerosis compared
with the general population; those who
had had a relapse; those with worse states
identified by a clinical measure (expanded
disability status scale (EDSS)). Relapses
have eVects over several months. Health
state valuations were higher than in the
general population. Costs were higher in
relapse than remission and for worse
EDSS states. IFâ-1b costs were larger
than cost savings. The best costeVectiveness estimate was £28 700 per
relapse avoided, which is £809 900 per
QALY gained; or £328 300 per QALY
gained allowing for eVects of progression
over 5 years. Estimates were robust to
changes in assumptions.
Conclusions—The impact of multiple
sclerosis on QoL is substantial. Future
trials should base outcomes measurement
on QoL and be better linked to natural
history and cost data. IFâ-1b produces
important occasional short term QoL
gains, but small gains in QALYs overall
and large additional costs.
(J Neurol Neurosurg Psychiatry 2000;68:144–149)
Keywords: costs; quality of life; multiple sclerosis; interferon â
Until recently, no specific therapy was available
for multiple sclerosis. After clinical trials which
established that interferon â preparations
reduce multiple sclerosis disease activity,1–4
three products have been licensed in the
United Kingdom—interferon â 1-b (IFâ-1b)
and two interferon â 1-a (IFâ-1a) compounds.
IFâ-1b is now also licensed for secondary progressive disease.5
At present, their role in clinical practice
remains uncertain. The trials are not easily
extrapolated to general patient populations and
provide no information about quality of life
eVects and cost-eVectiveness. The National
Health Service Executive’s health technology
assessment programme commissioned a 1 year
project to assess the cost-eVectiveness of
IFâ-1b (which at the time was the only licensed
product) in relapsing-remitting multiple sclerosis (RRMS).6 A cost-eVectiveness model was
constructed using published data on eVectiveness and the natural history of multiple sclerosis and new data on costs and quality of life.
There is a danger that cost-eVectiveness
summaries may suppress important detail; we
therefore examined the quality of life of people
with multiple sclerosis more closely than
economic appraisal strictly requires.
The cost-eVectiveness of IFâ-1b compared
with standard management was measured by
cost-eVectiveness and cost-utility ratios, defined respectively as cost per relapse avoided
and cost per quality adjusted life-year (QALY)
gained. This was based on the IFâ-1b trials’
reported clinical outcomes.1 2 However, resource use and quality of life and utilities (the
QALY adjustment weights) were not reported,
requiring collection of new data and a model to
link data from diVerent sources. The new data
could not directly compare patients receiving
and not receiving IFâ-1b, but provided a
means to generate such comparisons.
Two samples of people with RRMS were chosen from the catchment area of the neurology
service at Newcastle-Upon-Tyne: 40 patients
who had experienced a relapse in the 6 months
preceding a fixed date (the “recent relapse
group”); and 62 who had not (the “remission
group”). Subjects were chosen as they were
identified from medical records by a research
Our study only identified relapses via medical records and therefore had less detailed
information than the trial. Our definition of a
relapse (a new symptom or worsening of an
existing one) thus diVered from the trial, which
did not stipulate hospital management but
required evidence of new neurological abnormality. Hence, patients in our study may on
average have experienced more severe relapses.
Because this may lead to an overestimate of the
benefits of IFâ-1b, we tested the eVect of this
by sensitivity analysis.
Resource use data were collected by patient
questionnaire and medical records, and converted to NHS unit costs using various sources
(see costs section below). Quality of life data
were collected by patient questionnaire, and
converted to utilities using two sources. Firstly,
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Cost-eVectiveness of interferon â for multiple sclerosis
the EuroQoL-5 Dimension instrument,
EQ-5D7 was used in the patient questionnaires
(see quality of life section below), giving population based values via the measuring and valuing health (MVH) tariV developed at the University of York, UK.8 Secondly, utilities were
measured directly for 50 patients, 26 from the
recent relapse group and 24 from the remission
Linkage between multiple sclerosis natural
history data, trial outcomes, and cost and quality of life data was through the expanded
disability status scale (EDSS).9 As this is not
routinely collected, estimates were made for
those patients managed by the consultant neurologist (DB).
We reviewed available patient based measures
of QoL in multiple sclerosis, opting for the
multiple sclerosis quality of life 54 item scale
(MSQOL).10 This measure comprises a well
validated generic health status instrument, the
short form (SF)3611 and additional multiple
sclerosis specific items. It addresses 12 QoL
domains: physical and social function, roles
physical and emotional, pain, energy, mental
and general health, health distress, sexual
function, cognitive function, and overall QoL.
Composite scores for physical and mental
health can be calculated. As for the SF-36,
scores on the MSQOL range from 0–100, with
higher scores indicating better functioning
(0=worst possible, 100=best possible).
MSQOL has been shown in a United States
sample to have good psychometric properties10
(high internal consistency, test-retest reliability
and reproducibility; evidence of construct
validity). As the time frame set by the funding
body did not permit a pilot study to examine
the acceptability to patients of four detailed
sexual function items which might oVend some
and so reduce response rates, we omitted them
and included only the single item concerning
sexual satisfaction.
To support the use of this adapted version of
MSQOL, psychometric analysis using the
MAP-R multitrait scaling analysis package12
was performed. This showed that MSQOL
performs similarly for United Kingdom as for
United States patients; and its psychometric
properties were generally acceptable. Compared with United States patients, there were
marked ceiling eVects for two scales, role emotional and bodily pain; and marked floor eVects
for two scales, role physical and role emotional.
Floor eVects were particularly problematic for
the first, suggesting that MSQOL may underestimate marked diVerences in level of functioning in this domain between diVerent
patient subgroups. Full details of the psychometric analysis are reported elsewhere.6
We also collected the EQ-5D,7 a generic
measure with five dimensions—mobility, self
care, usual activities, pain/discomfort, and
anxiety/depression. The EQ-5D notation represents a composite health state denoting the
level of severity in each of the five health
domains. For example, 11112 means no problems with walking, self care, usual activities and
pain, moderate anxiety/depression; 22222
means moderate problems across all domains.
A summary quality of life score (varying
between 0 and 1) can then be assigned to each
state using the MVH tariV. The tariV was
derived from interviews with the United Kingdom general population, which involved asking
them to assign values to diVerent health states
using the time-trade oV method.13
The remission group judged quality of life in
remission by recording health status over time.
They kept a daily quality of life diary for 6
weeks, and at the start and end of this period
recorded via a structured questionnaire current
MSQOL and EQ-5D status. Because we could
not identify patients at the start of a relapse and
monitor them, relapses were assessed retrospectively. The recent relapse group recorded
in a structured questionnaire how they were
currently (MSQOL and EQ-5D) and how they
were at the worst of their relapse (EQ-5D). Up
to two 3 weekly reminders were sent to
In face to face interviews subjects valued multiple sclerosis specific health profiles, using the
time trade-oV method.13 These incorporated
quality of life eVects, described as EQ-5D
states, number of relapses, and the probability
of disease progression, taken from multiple
sclerosis natural history data14–17 and the
IFâ-1b trial. One scenario described multiple
sclerosis with no drug therapy, matching the
trial outcomes for the placebo group. Another
described multiple sclerosis with (unnamed)
drug therapy, matching the therapy group’s
outcomes. A third described more severe multiple sclerosis eVects without drug therapy.
Subjects also valued five EQ-5D profiles likely
to be encountered by patients with RRMS,
which could be directly compared with the
MVH values.
Service use data for 6 months were abstracted
from hospital case notes, including inpatient
stays (specialty, number of admissions, and
duration of stay), day cases and outpatient
visits (specialty and number of visits), drugs
(name, dosage, and duration), procedures and
tests (type and frequency), and appliances. The
patient questionnaires included questions on
primary and community services, recording
number of visits by professional group.
The Chartered Institute of Public Finance
and Accountancy (CIPFA) database18 provided inpatient and day case unit costs. Drug
costs were from the British National
Formulary19; IFâ-1b costs included administration and monitoring. Procedure and test
costs were from the Trust providing the
patients’ specialist service. Costs for appliances
and community services were taken from a
previous report.20
The IFâ-1b trial reported reduced numbers of
relapses but no statistically significant eVect on
disability. This requires a simple model which
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Parkin, Jacoby, McNamee, et al
Table 1 Demographic and clinical characteristics of participants in a survey of people
with relapsing-remitting multiple sclerosis
Type of respondent:
Age and sex:
Median age (range)
Employment status:
Unable to work
Disease duration:
<5 years
>5 years <10 years
>10 years
EDSS score:
Whole sample
No (%)
Utilities interview sample
No (%)
62 (61)
40 (39)
24 (48)
26 (52)
42 (25–65)
28 (28)
73 (72)
42 (28–65)
17 (34)
33 (66)
42 (42)
50 (51)
7 (7)
11 (22)
27 (54)
12 (24)
42 (42)
25 (26)
31 (32)
17 (33 )
17 (33 )
16 (33 )
33 (37)
32 (36)
24 (27)
13 (32)
18 (44)
10 (24)
Table 2 MSQOL mean scores for patients in remission and recently relapsing in a survey
of people with relapsing-remitting multiple sclerosis
In remission*
Mean (SD)
Recent relapse*
Mean (SD)
2 Tailed
p value†
Physical function (PF)
Role physical (RP)
Role emotional (RE)
Bodily pain (BP)
Mental Health (MH)
Energy/vitality (VT)
Health distress (HD)
Social function (SF)
Cognitive function (CF)
Sexual function (SX)
General health (GH)
Overall quality of life (QOL)
Change in health (TRANS)
Physical health composite score
Mental health composite score
42.9 (28.5)
39.9 (40.3)
64.3 (44.0)
73.1 (23.3)
69.4 (19.5)
39.9 (18.9)
59.2 (26.4)
66.2 (22.7)
70.1 (25.3)
59.6 (32.3)
43.2 (21.9)
69.5 (61.6)
47.9 (22.2)
43.9 (16.9)
63.5 (23.7)
20.0 (18.6)
13.2 (28.9)
53.5 (47.5)
58.6 (27.0)
63.7 (22.9)
32.0 (17.7)
48.8 (30.5)
47.5 (25.9)
60.8 (29.7)
46.1 (33.7)
39.0 (22.3)
49.9 (20.6)
31.9 (22.6)
32.8 (15.5)
55.6 (24.6)
*For each scale, a few patients did not complete suYcient items to permit computation. Bases on
which scale scores were calculated range from 53 to 60 for remission patients; from 38 to 40 for
relapse patients.
†Mann-Whitney Test
sums over time resultant cost savings and
QALY gains to compare with treatment costs.
However, because other trials may find an
impact on progression, a more complex model
is required which incorporates this and the
natural history of multiple sclerosis. It comprises a hypothetical cohort, within which each
patient is at any time at a particular EDSS
Table 3 MSQOL mean scores by expanded disability status scale (EDSS) scores in a
survey of people with relapsing-remitting multiple sclerosis
EDSS score
Mean (SD)
Mean (SD)
Mean (SD)
p Value†
Physical function (PF)
Role physical (RP)
Role emotional (RE)
Bodily pain (BP)
Mental health (MH)
Energy/vitality (VT)
Health distress (HD)
Social function (SF)
Cognitive function (CF)
Sexual function (SX)
General health (GH)
Overall quality of life (QOL)
Change in health (TRANS)
Physical health composite score
Mental health composite score
54.2 (29.8)
44.8 (43.0)
67.8 (44.0)
67.7 (23.8)
71.6 (17.5)
39.3 (17.5)
64.3 (24.7)
65.7 (26.2)
71.3 (25.9)
69.8 (31.6)
42.1 (21.8)
79.3 (85.1)
48.3 (27.0)
45.4 (18.2)
67.5 (24.2)
25.9 (20.9)
19.2 (29.1)
55.9 (46.7)
65.2 (26.1)
67.1 (19.5)
36.6 (19.7)
56.3 (29.9)
56.9 (23.1)
67.9 (23.7)
48.3 (27.5)
37.9 (21.5)
53.6 (19.1)
39.8 (20.9)
36.1 (15.7)
59.3 (22.9)
12.6 (12.0)
15.8 (37.5)
45.6 (48.7)
65.2 (28.3)
59.8 (26.8)
35.3 (21.1)
39.3 (28.6)
41.7 (23.3)
54.3 (32.5)
42.9 (37.2)
38.6 (25.3)
49.9 (22.9)
34.5 (24.3)
31.2 (15.9)
49.9 (24.5)
*For each scale, a few patients did not complete suYcient items to permit computation. Bases on
which scale scores were calculated range from 26 to 30 for patients with EDSS of 0–3; from 29 to
32 for patients with EDSS of 3.5–5.5; from 19 to 21 for patients with EDSS of 6 and over.
†Kruskal-Wallis 1 way ANOVA.
level, initially EDSS 3, the average trial
baseline. Progression probabilities, taken from
the natural history literature, determine the
levels in subsequent years; a reduced risk rate,
taken from trial estimates, applies to those having therapy. Each patient’s illness career is
summarised as a “transition state”— for example, EDSS 3→3 (no progression), EDSS 3→5
(initially EDSS 3, finally EDSS 5), which has a
particular level of costs and utility, calculated
as an average for each EDSS level weighted by
the time spent in it. Full details of the model
are reported elsewhere.6
Relapse costs and utility losses were the difference in average cost and EQ-5D scores
between remission and relapse groups. The
remission group provided EDSS level costs. A
utility score was calculated for each EDSS level
by assigning each patient’s EQ-5D state in
remission a score from the MVH tariV and
averaging for those at that level.
Analysis of health state diVerences between
remission and relapse patients are reported as
two tailed p values using Mann-Whitney tests.
Analysis of EDSS scores are reported using
Kruskal-Wallis one way analysis of variance
(ANOVA). All statistical tests were performed
using SPSS software.
Table 1 summarises demographic and clinical
characteristics. Most patients were women and
the average age was 42 years. Half could not
work because of long term illness or disability
(55% of the recent relapse group, 47% of the
remission group). Eighty nine were assigned
EDSS scores; 37% scored 0–3, 36% scored
4–5, 27% scored 6 or more; the remaining 13
patients’ notes could not be obtained in the
time in which data were collected. Except for
employment status, the utilities subsample had
similar sociodemographic and clinical characteristics compared with the whole sample.
Table 2 shows MSQOL scores for remission
and relapse groups. Scores were significantly
diVerent (p<0.001) for physical function, role
physical, and social function scales, the change
in health item, and the physical health
composite. As we do not reproduce MSQOL
here, it may aid interpretation to know that for
physical function, lower scores represent reduced ability to perform a range of gentle
through to vigorous physical activities; for role
physical, lower scores indicate problems in
carrying out work and other regular daily
activities; and for social function, lower scores
indicate problems in carrying out normal social
activities with family and friends. Scores for
emotional problems, mental health, cognitive
function, and general health perceptions
showed least diVerences. Table 3 reports
MSQOL scores for EDSS subgroups. There
was a highly significant trend in physical function scores, from 54.2 with an EDSS score <3
to 12.6 with a score >6 (p<0.0001). There
were also significant diVerences for social and
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Cost-eVectiveness of interferon â for multiple sclerosis
Table 4 Utility values of disease specific scenarios and
EQ-5D states from participants in a survey of people with
relapsing-remitting multiple sclerosis
Disease specific scenarios:
EQ-5D states:
Mean MVH
NA=Not applicable.
sexual function (p<0.01) and role physical and
health distress (p=0.01). There were small but
significant diVerences for both composite
Subjects had markedly lower SF-36 scores
than a “normative” United Kingdom general
population.21 For example, they scored 45
points lower on the physical function scale and
43 lower on the role physical scale than the
general population with long standing illnesses;
and 59 and 62 respectively lower than those
without. DiVerences were smaller but none the
less considerable for social function, energy,
and general health.
Ninety six respondents completed all five
EQ-5D statements. Only 5% were currently in
state 11111, compared with 57% of a general
population.22 Only 27 out of a possible 243
states were found; 31 patients reported problems with mobility and 32 problems with
performing usual activities. The recent relapse
group had worse mobility, self care, and pain
than the remission group but similar anxiety
and depression levels. The recent relapse
Table 5
Cost, quality adjusted life-year, and cost eVectiveness estimates from diVerent models
Standard care
5 Year model with no eVect on progression
Undiscounted costs:
Total costs
Cost per relapse avoided
Discounted costs:
Total cost
Cost per relapse avoided
QALY gain:
Cost per QALY gained:
Costs only discounted
Costs and QALYs discounted
5 Year model with eVect on progression
QALY gain
Cost per QALY gained
10 Year model with eVect on progression: base case
QALY gain
Cost per QALY gained
10 Year model with eVect on progression: best case
QALY gain
Cost per QALY gained
10 Year model with eVect on progression - worst case
QALY gain
Cost per QALY gained
Drug therapy
group’s profile was significantly poorer in all
domains during relapse than currently.
Table 4 shows mean utility scores. The IFâ-1b
and placebo scenario scores were very similar,
but the severe scenario scored much lower.
Compared with the MVH study, the EQ-5D
scores were consistently higher, with greater
diVerences among more severe states.
The results enabled conversion of EDSS
scores into utilities. The MVH values were
applied to each patient’s EQ-5D state, from
which the mean value for each studied EDSS
level was calculated: 0.71 for EDSS 3, 0.66 for
EDSS 4, 0.52 for EDSS 5, 0.49 for EDSS 6,
and 0.35 for EDSS 7. Similarly, the utility loss
from relapse was calculated by averaging over
subjects the MVH values for each EQ-5D state
in remission and relapse, and taking the diVerence: average remission value=0.604; average
relapse value=0.136; a net loss of 0.468 per
Average costs were £529 in the remission
group and £2644 in the recent relapse group,
giving relapse costs of £2115 per patient. The
diVerence was mainly related to use of
inpatient and day case and, to a lesser extent,
community services, with no diVerence in outpatient visits, drugs, tests, and appliances.
Higher resource use was associated with higher
EDSS scores.
Table 5 summarises results obtained from the
models, showing costs, benefits, and costeVectiveness and cost-utility ratios (rounded to
the nearest £100). The results including only
the eVect of relapses are presented with and
without discounting at the United Kingdom
Government recommended rate of 6%, although discounting makes little diVerence.
IFâ-1b reduced relapses by 1.52 per patient
over 5 years, but had discounted net costs of
£43 600, giving a cost-eVectiveness ratio of
£28 700 per relapse avoided. There was a gain
of 0.054 discounted QALYs, giving a costutility ratio of £809 900 per QALY gained.
The more complex models, incorporating
progression changes, are presented only in discounted form. For a five year model, 0.13
QALYs were gained at a cost of £43 400, giving £328 300 per QALY gained. The robustness of this was tested using one way sensitivity
analyses. The figure shows that varying the
assumptions for a range of variables produced
no important changes in the cost-utility ratio.
The largest change was related to the frequency
of relapses.
A 10 year model, which uses more assumptions and has greater uncertainty, produced
similar results using base case assumptions,
and was examined further by altering the
assumptions to favourable (“best case”) assumptions about progression and IFâ-1b
eVectiveness and unfavourable (“worst case”)
assumptions, equivalent to “no impact on pro-
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Parkin, Jacoby, McNamee, et al
500 000
587 600
Cost per QALY gained (£)
450 000
431 600
400 000
380 000
379 000
366 300
350 000
300 000
328 500
329 200
326 400
326 700
341 100
318 200
295 500
283 200
250 000
231 700
200 000
223 800
176 500
150 000
Sensitivity analysis of 5 year model. Base case and lower and upper estimates are: discount rate 6% (0–10); EDSS costs per year: EDSS 3 £740
(£370-£1480), EDSS 4 £850 (£425-£1700), EDSS 5 £1570 (£785-£3140), EDSS 6 £1590 (£795-£3180); EDSS utilities: EDSS 3 0.71
(0.65–0.79), EDSS 4 0.66 (0.59–0.74), EDSS 5 0.52 (0.41–0.67), EDSS 6 0.49 (0.38–0.63); IFb-1b costs per year £10 500 (£6000 - £12 000);
IFb-1b transition probabilities: EDSS 3→4 0.12 (0.20–0.10), EDSS 3→5 0.06 (0.10–0.05), EDSS 3→6 0.22 (0.10–0.25); Relapse cost £2115
(£1000–£3000); Relapse duration in weeks 4 (2–6); utility loss per relapse 0.5 (0.25–0.75); Number of relapses with IFb-1b 3.71 (2.5–5).
gression”. The best case gave £74 500 per
QALY gained compared with base case and
worst case values of £228 300 and £604 600
respectively (table 5).
Discussion and conclusions
IFâ-1b produces important occasional short
term quality of life gains, but because they are
infrequent they translate into small QALY
gains. Even optimistic estimates of longer term
gains from delayed progression produce small
aggregate QALY gains because few benefit.
With large net costs, IFâ-1b has a high cost per
QALY gained.
It is diYcult to compare these results with
other studies as, to our knowledge, no previous
economic evaluation of interferon â therapy
has been undertaken using similar methods. A
Canadian study calculated comparable cost per
relapse avoided ratios of between Can$48 000Can$67 000.23 However, no attempt was made
to translate these eVects into QALYs.
This study required many assumptions to
construct an economic evaluation from clinical
trials designed for a diVerent purpose. Key
instruments for data collection were developed
rapidly, some data were collected retrospectively, and data collection was not planned to
usual statistical specifications. However, the
assumptions are evidence based, plausible, and
robust to testing. The data instruments performed well and the results seem conclusive
within a large margin of uncertainty.
Extensive sensitivity analysis was conducted
to ensure that the results could be generalisable
to a wide patient population. This was particularly important as our study sample exhibited
some clinical diVerences from the drug trial
population with respect to EDSS levels and the
measurement of relapses. In addition, we made
no attempt to value indirect costs, such as time
lost from work and other activities for patients
and carers. Although these are likely to have
important implications for the level of costs
associated with EDSS scores and relapses, we
have shown that diVerent values make little
diVerence to the cost/QALY gain ratio (figure
and table 5).
Summary eVectiveness measures such as
relapse rates or EDSS progression may mask
important quantifiable eVects of multiple sclerosis on quality of life. Measures of QoL are
consistent with EDSS scores, which is important as they are widely used by clinicians, but
provide important additional information. The
outcome measure of choice in evaluations of
therapies for multiple sclerosis should therefore
be changes in QoL. Such studies must also link
outcomes with direct and indirect costs, which
has implications for trial design.
These results should help those making prescribing and policy decisions at diVerent levels.
Patients and clinicians might consider the
extent of the quality of life gains produced by
IFâ-1b compared with alternatives for improving health. Third party payers have also to consider potential health gains for people with
other conditions which could result from alternative uses of IFâ-1b expenditure, bearing in
mind both eYciency, as indicated by the costutility figures, and also equity.
This project was funded by the NHS Health Technology
Assessment programme, project number 95/01/2. The views
and opinions expressed do not necessarily reflect those of the
Department of Health. The following were members of the
team that carried out the study at the University of Newcastle
Upon Tyne: Ms Julie Doughty, junior research associate, Centre
for Health Services Research; Sister Joanna Forsyth, staV nurse,
Department of Clinical Neurology; Mrs Sylvia Hudson, project
secretary, Centre for Health Services Research. We are grateful
to the people who gave their time to take part in our surveys, to
Paul Dolan and Karen Gerard for help with the valuation exercise, to Pippa Anderson for access to psychometric analysis
software, and to referees of our report to the HTA for their
helpful comments.
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Cost-eVectiveness of interferon â for multiple sclerosis
6 Parkin D, McNamee P, Jacoby A, et al. A cost-utility analysis of interferon â for multiple sclerosis. Health Technology
Assessment 1998;2:1–58.
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calculations. York: University of York, Centre for Health
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sclerosis: an expanded disability status scale (EDSS). Neurology 1983;33:1444–52.
10 Vickrey BG, Hays RD, Harooni R, et al. A health-related
quality of life measure for multiple sclerosis. Qual Life Res
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Med Care 1992;30:473–83.
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Clinical course and disability. Brain 1989;112:133–46.
15 Weinshenker BG, Bass B, Rice GPA, et al. The natural history of multiple sclerosis: a geographically based study. ii.
Gowers’ sign
Sir William Richard Gowers (1845–1915) is a
name hallowed in the minds of most neurologists as one of the great Victorian founders of
our discipline. He is probably best remembered for the remarkable manual first published in 1886, still a continual source of
reference and wisdom, remarkable for its
wealth of clinical detail, experience, and
understanding. Even more remarkable is it
when we realise that there was virtually no
neurochemistry, minimal electrophysiology,
and of course only the most fundamental
radiology and neuropathology available to
His name is preserved in several eponymous
conditions, though paradoxically he inveighed
about of the use of eponyms:
“Scientific nomenclature should be itself
scientific, not founded upon accidents.
However anxious we may be to honour
individuals, we have no right to do so at
the expense of the convenience of all
future generations of learners.”
Gowers’ phenomenon, Gowers’ distal myopathy, Gowers’ solution in the treatment of
migraine, Gowers’ anterior spinocerebellar
tract, are the best known eponyms. There are
three Gowers’ signs: Pain along the compressed sciatic nerve on passive dorsiflexion of
the foot; the irregular contraction of the pupil
in early tabes (cf Argyll Robertson); and the
climbing up the legs signs in Duchenne
Predictive value of the early clinical course. Brain
16 Weinshenker BG, Rice GPA, Noseworthy JH, et al. The
natural history of multiple sclerosis: a geographically based
study. iii. Multivariate analysis of predictive factors and
models of outcome. Brain 1991;114:1045–56.
17 Weinshenker BG, Rice GPA, Noseworthy JH, et al. The
natural history of multiple sclerosis: a geographically based
study. iv. Applications to planning and interpretations of
clinical therapeutic trials. Brain 1991;114:1057–67.
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23 Canadian Coordinating OYce for Health Technology
Assessment. Interferon â-1b and multiple sclerosis. Ottawa:
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It is the last which I highlight here, as a
masterly example of clinical description.1 A
detailed account of the progressive course and
family history, pattern of weakness of muscles,
the pseudohypertrophy and his experience of
the pathology precede it. He gives full credit
to the earlier work of Meryon2 3 and
“The diYculty in going upstairs is especially due to the weakness of the extensors
of the knee and hip. The defect of the
extensors of the hip causes the gait to have
a peculiar oscillating characters.
The greatest defect, however, is in the
power of rising from the floor, and the
most characteristic peculiarity is the mode
in which this is achieved, if it be still possible, and no objects near, by which the
patient can aid himself. He commonly has
not suYcient power to extend the knees
when the weight of the trunk is on the
upper extremity of the femur, which is
then a lever in which power, applied
between the fulcrum and the weight, acts
at least advantage. He therefore places his
hands on his knees, his arms thus bring
much of the weight of the upper part of
the trunk on the femur close to the
fulcrum, between this and the power,
which can then act at greater advantage.
When the knees are extended, the power
of the extensors of the hip may be
suYcient to raise the body into the
upright position, or the patient may aid
them by an upward push with the hand as
he takes it oV. If, however, these extensors
are weak, the hands are often moved
higher and higher up the thighs, grasping
alternately, and thus pushing up the
trunk. To get thus the requisite support,
the knees must not he quite extended, and
if their extensors have no power, the device
cannot be employed, and the patient is
altogether unable to rise. In many cases,
especially when extension of the hip is
easy, the patient achieves the extension of
the knees in another way; he puts the
hands on the ground, stretches out the legs
behind him far apart, and then, the chief
weight of the trunk resting on the hands,
by keeping the toes on the ground and
pushing the body backwards, he manages
to get the knees extended, until the trunk
is supported by the hands and feet, all
placed as widely apart as possible. Next
the hands are moved alternately along the
ground backwards, so as to bring a larger
portion of the weight of the trunk over the
legs. Then one hand is placed upon the
knee, and a push with this, and with the
other hand on the ground, is suYcient to
enable the extensors of the hip to bring the
trunk into the upright position.”
This exemplary description is illustrated by
several excellent drawings, from his own hand,
which show the same mastery of simple precision and clear exposition that characterise all
his writings.
304 Beverley Road, Anlaby, Hull HU10 7BG,
York, UK
1 Gowers WR. A manual of disease of the nervous
system. London: Churchill, 1886;1:391–4.
2 Meryon E. On fatty degeneration of the
voluntary muscles. Lancet 1851;ii:588–9.
3 Meryon E. On granular and fatty degeneration
of the voluntary muscles. Medico-Chirurgical
Transactions 1852;35:73–84.
4 Duchenne GBA Recherches sur la paralysie
musculaire pseudo-hypertrophique, ou paralysie myo-sclérosique. Archives Génerales de Médicine 1868;6:5–25; 179–209,305–21; 421–43;
Downloaded from jnnp.bmj.com on September 9, 2014 - Published by group.bmj.com
Treatment of multiple sclerosis with interferon
β: an appraisal of cost-effectiveness and
quality of life
David Parkin, Ann Jacoby, Paul McNamee, et al.
J Neurol Neurosurg Psychiatry 2000 68: 144-149
doi: 10.1136/jnnp.68.2.144
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